Dialkyl azodicarboxylates 4+4 cycloaddition

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

Cycloaddition reactions of aziridines with a wide assortment of dipolarophiles have been studied. The reaction of dialkyl azodicarboxylates with the cf5-aziridine (27) is stereospecific... 

No cycloaddition has been found to occur in the reaction of several indolizines with tetracyanoethylene, substitution occurring instead in the 1- and 3-positions (78JHC1471). Similar products have been formed in the reactions of 2-methylindolizine with nitroethane, yielding (86) (79JPS321), and of indolizines with dialkyl azodicarboxylates, which gave a mixture of (87) and (88) (80TL3673, 79H(12)787>. 

The 4,5-double bond of 2(3//)-oxazolones participates in thermal [4 + 2] cycloaddition reactions. With dialkyl azodicarboxylates the addition occurs at 80 C to give the cycloadducts 430 (Scheme 97). With a chiral substituent attached to N(3), diastereoselectivities as high as 72% can be obtained. Cycloadditions with cyclopentadiene or benzofuran require higher temperatures and longer reaction times, but can yield highly efficient chiral oxazolidin-2-one auxiliaries. 

Cycloaddition Reactions of Dialkyl Azodicarboxylates and of 1,2,4-Triazole-3,5-diones... 

In other examples of the use of azo compounds in pyridazine synthesis, dialkyl azodicarboxylates undergo cycloaddition with dienes to give 1,2,3,6-tetrahydropyridazines. Azobis(formamidine) reacts similarly. Diethyl azodicarboxylate also reacts with furans to give an adduct which is transformed into a pyridazine by acid. In a photochemical synthesis,... 

Cycloaddition reaction of 2-vinylpyridines and dialkyl azodicarboxylates in boiling benzene gave two isomeric 1 1 adducts. The minor products were identified as pyrido[l, 2-c][l, 2,3]triazine diesters (101) (Equation (13)) <78TL273i, 79T2027). When the cycloaddition reaction was performed in the presence of biocatalyst Saccharomyces cerevisiae), no (101) was formed <93BCJ2429>. 

The A -1,3,4-thiadiazolidines (148) undergo cycloaddition with diethyl azodicarboxylate stereospecifically, forming 2,5-dialkyl-3,4-diethoxy-carbonyl-1,3,4-thiadiazolidines (154) with complete retention of configuration. The comparable stereospecific cycloaddition involving dimethyl acetylenedicarboxylate, (152) (153), yields the corresponding 2,5-dihy drothiophens. ... 

---